There are several components of the research program. Component 1: Platelet Biology, Reactivity and Genomics. Utilizing one of the largest human samples (FHS: Framingham Heart Study) with platelet reactivity we have conducted deeper genetic scans for contributing genes. These scans use new genetic maps with deeper coverage of rare variation. DNA genotyping of an additional diverse population sample, the FHS OMNI cohort, was supported allowing additional validation samples and gene coverage for platelet reactivity traits. Further support was provided for genotyping of the U.K.-based Caerphilly Study in Men cohort, a rich study repository of hemostatic factor and platelet reactivity trait data. New genetic studies in 2015 led by the lab expanded the SNP platforms and imputation used to study platelet traits. A large effort to study the genetics of PLT (platelet count) and MPV (mean platelet volume) in up to >130,000 individuals had yielded many new gene discoveries. Targeted qPCR RNA measurements in FHS platelet samples are also completed and underway to investigate mechanistic questions for specific candidate genes. One of the largest epidemiological studies of PLT and MPV and their association with CVD risk factors was completed in FHS ref 1. Separately, platelet RNA samples were collected from 32 myocardial infarction samples and whole transcriptome RNA sequencing led to identification of novel genes associated with different platelet factors and CVD diagnoses ref 2. Additional cell line and anonymous tissue samples were purchased to augment this work with future RNA sequencing. In 2015 the Lab began work on a new Platelet OMICs resource to be publicly released and also utilized in the Lab's research in this field. Component 2: Tissue-specific Gene Expression. A major cell- and tissue-specific database of genetic factors on gene expression (eQTLs) was maintained and updated. This catalog was used to add information on genes to many disease and risk factor studies, primarily in the cardiovascular and metabolic disease domains. In a separate project, gene expression measurements in whole blood samples from >5,300 FHS samples were employed in studies to identify genes whose RNA levels correlated with traits, including new eQTLs and splice (sQTLs) ref 3. A major study was undertaken to integrate FHS gene expression data with data on 15,000 other samples. This led the identification and validation of >1,200 genes whose RNA levels change during aging, recently accepted for publication. Research was supported to conduct experiments knocking out some of these novel genes in the worm C. elegans and D. melanogaster in order to assess whether they significantly affect lifespan. Component 3: Development and Application of Bioinformatics Resources. Beyond the eQTL database mentioned above, a large genome-wide association study (GWAS) results database GRASP ref. 4 was updated, and an online NIH query site developed. The database is publicly downloadable and queryable at the URL: grasp.nhlbi.nih.gov/Overview.aspx. This database of results was expanded in early FY15 to 2,100 GWAS articles ref. 5 and is undergoing an additional expansion in FY16. The database was widely used in addressing many research questions as evidenced by thousands of web hits and queries per month and citations to related publications.